I've still not scrutinized the DFRPG PDFs, but while perusing tonight I noticed a box on p. 36 of "Exploits" which says clearly and without caveat, "Whether you attack once or several times, all attacks involving your 'off' hand are at -4."

For years I've ignored off-hand penalties for trained, unarmed strikes (and will continue to do so), but I thought this a fairly important detail to mention as it has spawned quite a few forum threads over the years.

That box is in the section for Melee [weapon] attacks. A few pages later, in the section for Unarmed Combat, no mention is made of off-hand but in Adventurers under Unarmed skills it says explicitly that there is no off-hand penalty for trained unarmed punches. No mention under Unarmed Grappling skills however.

In my 'defense,' the box is on and reads as though still part of the general preamble of the "Attacks" main header. The section "Melee Attacks" doesn't start until p. 37, and shares a sub-heading with "Unarmed Combat" on p. 38 and "Ranged Attacks" on p. 41.

But at any rate, the Ambidexterity advantage on p. 47 of "Adventurers" says "Most people... suffer -4 to DX when fighting..." (not to a trained skill like Karate or Brawling, but to DX), and as you noted, the "Unarmed Striking Skills" section on p. 93 explicitly says there's no off-hand penalty for unarmed strikes. (I would assume the same grappling).

So, the mystery that didn't exist until I made it one is "solved." Thank you (and DFRPG) for clarifying!

I'm honestly not sure. Gun shy, I will probably stay out of any further DFRPG rules parsing until A) I've read its entirety, B) I have more experience GMing it, and C) y'all have already hammered out the details, heh heh.

Exploits:
Melee Attacks section refers to pg 95 for Melee modifiers
pg 95 states off-hand mod for attacks
Unarmed combat says unarmed follows same rules as Melee and same modifiers and then lists differences, none of which mention off-hand penalties

Defense rolls refers to tables on pg 96-97 which lists off-hand -2
Parrying section lists off-hand
What am I parrying with? says off-hand -2
None of these list an exception for unarmed
Unarmed parries section doesn't mention off-hand one way or the other

Adventurers:
Ambidexterity says most fighters are at -4 DX with their off hand unless you have this.
Unarmed striking skills says no off-hand penalty to punch with off-hand with these skills, does not mention parries (afaict, the only mention of off-hand specifically with unarmed skills i can find)
Unarmed grappling skills makes no mention of off-hand whatsoever

My interpretation of RAW:
No off-hand penalty for attacking or defending with unarmed striking skills
Off-hand penalty for attacking with unarmed grappling skills and strikes using DX

As to whether this is RAI, beats me.

How I'm going to run it? Probably no off-hand for any unarmed learned skills - unarmed combat is rough enough as it is - off-hand penalties if fighting unarmed using DX

While I like the new ruleset quite a bit - I love the new rules/simplification for Slams, Surprise and some others, this disappointed me. I was hoping this would be clearer but seems somewhat contradictory.

I've still not scrutinized the DFRPG PDFs, but while perusing tonight I noticed a box on p. 36 of "Exploits" which says clearly and without caveat, "Whether you attack once or several times, all attacks involving your 'off' hand are at -4."

For years I've ignored off-hand penalties for trained, unarmed strikes (and will continue to do so),